tbuckley/cabot-search huggingface dataset:
Outbreak of <i>Burkholderia stabilis</i> Infections Associated with Contaminated Nonsterile, Multiuse Ultrasound Gel — 10 States, May–September 2021
Authors: Matthew J. Hudson, Stacy C. Park, Amy Mathers, Hardik Parikh, Janet Glowicz, David Dar, Marjan Nabili, John J. LiPuma, Amy Bumford, Matthew A. Pettengill, Mark R. Sterner, Julie Paoline, Stacy Tressler, Tiina Peritz, Jane Gould, Stuart R. Hutter, Heather Moulton-Meissner, Kiran M. Perkins
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

In July 2021, the Virginia Department of Health notified CDC of a cluster of eight invasive infections with Burkholderia stabilis, a bacterium in the Burkholderia cepacia complex (BCC), among hospitalized patients at hospital A. Most patients had undergone ultrasound-guided procedures during their admission. Culture of MediChoice M500812 nonsterile ultrasound gel used in hospital A revealed contamination of unopened product with B. stabilis that matched the whole genome sequencing (WGS) of B. stabilis strains found among patients. CDC and hospital A, in collaboration with partner health care facilities, state and local health departments, and the Food and Drug Administration (FDA), identified 119 B. stabilis infections in 10 U.S. states, leading to the national recall of all ultrasound gel products produced by Eco-Med Pharmaceutical (Eco-Med), the manufacturer of MediChoice M500812. Additional investigation of health care facility practices revealed frequent use of nonsterile ultrasound gel to assist with visualization in preparation for or during invasive, percutaneous procedures (e.g., intravenous catheter insertion). This practice could have allowed introduction of contaminated ultrasound gel into sterile body sites when gel and associated viable bacteria were not completely removed from skin, leading to invasive infections. This outbreak highlights the importance of appropriate use of ultrasound gel within health care settings to help prevent patient infections, including the use of only sterile, single-use ultrasound gel for ultrasonography when subsequent percutaneous procedures might be performed.
Hospital policies can create barriers to good management of opioid withdrawal
Authors: Helen Saul, Deniz Gursul, Brendan Deeney, Magdalena Harris, Adam Holland
Journal: BMJ (2022)

The studyHarris M, Holland A, Lewer D, et al. Barriers to management of opioid withdrawal in hospitals in England: a document analysis of hospital policies on the management of substance dependence. BMC Med 2022;20:151.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/many-hospital-policies-create-barriers-to-good-management-of-opioid-withdrawal/.
Forecasting immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor t-cell therapy
Authors: Yalda Amidi, Christine A Eckhardt, Syed A Quadri, Preeti Malik, Marcos Santana Firme, Daniel K Jones, Aayushee Jain, Husain H Danish, Daniel B Rubin, Caron A Jacobson, Sydney S Cash, Jong Woo Lee, Jorg Dietrich, M Brandon Westover
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Immune effector cell-associated neurotoxicity syndrome (ICANS) is a clinical and neuropsychiatric syndrome that can occur days to weeks following administration chimeric antigen receptor (CAR) T-cell therapy. Manifestations of ICANS range from encephalopathy and aphasia to cerebral edema and death. Because the onset and time course of ICANS is currently unpredictable, prolonged hospitalization for close monitoring following CAR T-cell infusion is a frequent standard of care. Methods This study was conducted at Brigham and Women’s Hospital from April 2015 to February 2020. A cohort of 199 hospitalized patients treated with CAR T-cell therapy was used to develop a combined hidden Markov model and lasso-penalized logistic regression model to forecast the course of ICANS. Model development was done using leave-one-patient-out cross validation. Results Among the 199 patients included in the analysis 133 were male (66.8%), and the mean (SD) age was 59.5 (11.8) years. 97 patients (48.7%) developed ICANS, of which 59 (29.6%) experienced severe grades 3–4 ICANS. Median time of ICANS onset was day 9. Selected clinical predictors included maximum daily temperature, C reactive protein, IL-6, and procalcitonin. The model correctly predicted which patients developed ICANS and severe ICANS, respectively, with area under the curve of 96.7% and 93.2% when predicting 5 days ahead, and area under the curve of 93.2% and 80.6% when predicting the entire future risk trajectory looking forward from day 5. Forecasting performance was also evaluated over time horizons ranging from 1 to 7 days, using metrics of forecast bias, mean absolute deviation, and weighted average percentage error. Conclusion The forecasting model accurately predicts risk of ICANS following CAR T-cell infusion and the time course ICANS follows once it has begun.Cite Now
Final results from TAIL: updated long-term efficacy of atezolizumab in a diverse population of patients with previously treated advanced non-small cell lung cancer
Authors: Andrea Ardizzoni, Sergio Azevedo, Belen Rubio-Viqueira, Delvys Rodriguez-Abreu, Jorge Alatorre-Alexander, Hans J M Smit, Jinming Yu, Konstantinos Syrigos, Elen Höglander, Monika Kaul, Jonathan Tolson, Youyou Hu, Hans Kristian Vollan, Thomas Newsom-Davis
Journal: Journal for ImmunoTherapy of Cancer (2022)

In patients with previously treated advanced or metastatic non-small cell lung cancer (NSCLC), atezolizumab therapy improves survival with manageable safety. The open-label, single-arm phase III/IV TAIL study ( NCT03285763 ) evaluated atezolizumab monotherapy in patients with previously treated NSCLC, including those with Eastern Cooperative Oncology Group performance status of 2, severe renal impairment, prior anti-programmed death 1 therapy, autoimmune disease, and age ≥75 years. Patients received atezolizumab intravenously (1200 mg) every 3 weeks. At data cut-off for final analysis, the median follow-up was 36.1 (range 0.0–42.3) months. Treatment-related (TR) serious adverse events (SAEs) and TR immune-related adverse events (irAEs) were the coprimary endpoints. Secondary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate, and duration of response. Safety and efficacy in key patient subgroups were also assessed. TR SAEs and TR irAEs occurred in 8.0% and 9.4% of patients, respectively. No new safety signals were documented. In the overall population, median OS and PFS (95% CI) were 11.2 months (8.9 to 12.7) and 2.7 months (2.3 to 2.8), respectively. TAIL showed that atezolizumab has a similar risk-benefit profile in clinically diverse patients with previously treated NSCLC, which may guide treatment decisions for patients generally excluded from pivotal clinical trials.
Cholera in Haiti, Again
Authors: Richard P. Wenzel
Journal: New England Journal of Medicine (2022)

policymakers curtail the power of health care monopolies to drive up costs and do more to limit health care prices across our array of public and private coverage systems, virtually everyone's access to affordable care is at risk.Our patchwork system of health coverage is not going away anytime soon.However, the primary reason millions of Americans remain uninsured or have insurance coverage that leaves them financially exposed is the high costs in our health care system.Constraining the growth of costs while reducing inequities in access and outcomes will require new but difficult reforms.
Mask Wars
Authors: Debra Malina, J. Alexander Navarro, Christopher McKnight Nichols, Bruno J. Strasser, Meng Zhang
Journal: New England Journal of Medicine (2022)

This documentary video explores the controversies surrounding masks and mask mandates throughout the centuries. The changing perceptions of masking leading up to the Covid-19 pandemic are discussed. This video is based on a Graphic Perspective by David S. Jones, M.D., Ph.D., and Scott H. Podolsky, M.D. (Mask Wars, in the September 23, 2021, issue).
Resurgence of Cholera in Haiti amidst Humanitarian Crises
Authors: Karine Severe, Nadalette Alcenat, Vanessa Rouzier
Journal: New England Journal of Medicine (2022)

was ultimately transmitted to other countries in Latin America, 4 a third potential explanation is that the current strain could have been reintroduced to Haiti from a nearby country; however, this explanation is less likely than the others, given the phylogenetic evidence and the absence of recent cholera cases in the region.These findings, along with the resurgence of cholera in several parts of the world 5 despite available tools to fight it, suggest that cholera control and prevention efforts must be redoubled.
Tecovirimat for Monkeypox in Central African Republic under Expanded Access
Authors: Festus Mbrenga, Emmanuel Nakouné, Christian Malaka, Josephine Bourner, Jake Dunning, Guy Vernet, Peter Horby, Piero Olliaro
Journal: New England Journal of Medicine (2022)

Tecovirimat for Monkeypox in Africa Tecovirimat is an antiviral agent used to treat monkeypox. In this report, its use as part of an expanded access program in the Central African Republic is reported.
Prokaryotic and viral genomes recovered from 787 Japanese gut metagenomes revealed microbial features linked to diets, populations, and diseases
Authors: Yoshihiko Tomofuji, Toshihiro Kishikawa, Yuichi Maeda, Kotaro Ogawa, Yuriko Otake-Kasamoto, Shuhei Kawabata, Takuro Nii, Tatsusada Okuno, Eri Oguro-Igashira, Makoto Kinoshita, Masatoshi Takagaki, Naoki Oyama, Kenichi Todo, Kenichi Yamamoto, Kyuto Sonehara, Mayu Yagita, Akiko Hosokawa, Daisuke Motooka, Yuki Matsumoto, Hidetoshi Matsuoka, Maiko Yoshimura, Shiro Ohshima, Shinichiro Shinzaki, Shota Nakamura, Hideki Iijima, Hidenori Inohara, Haruhiko Kishima, Tetsuo Takehara, Hideki Mochizuki, Kiyoshi Takeda, Atsushi Kumanogoh, Yukinori Okada
Journal: Cell Genomics (2022)
Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines
Authors: Byungji Kim, Ryan R. Hosn, Tanaka Remba, Dongsoo Yun, Na Li, Wuhbet Abraham, Mariane B. Melo, Manuel Cortes, Bridget Li, Yuebao Zhang, Yizhou Dong, Darrell J. Irvine
Journal: Journal of Controlled Release (2022)

The recent clinical success of multiple mRNA-based SARS-CoV-2 vaccines has proven the potential of RNA formulated in lipid nanoparticles (LNPs) in humans, and products based on base-modified RNA, sequence-optimized RNA, and self-replicating RNAs formulated in LNPs are all in various stages of clinical development. However, much remains to be learned about critical parameters governing the manufacturing and use of LNP-RNA formulations. One important issue that has received limited attention in the literature to date is the identification of optimal storage conditions for LNP-RNA that preserve long-term activity of the formulations. Here, we analyzed the physical structure, in vivo expression characteristics, and functional activity of alphavirus-derived self-replicating RNA (repRNA)-loaded LNPs encoding HIV vaccine antigens following storage in varying temperatures, buffers, and in the presence or absence of cryoprotectants. We found that for lipid nanoparticles with compositions similar to clinically-used LNPs, storage in RNAse-free PBS containing 10% (w/v) sucrose at −20 °C was able to maintain vaccine stability and in vivo potency at a level equivalent to freshly prepared vaccines following 30 days of storage. LNPs loaded with repRNA could also be lyophilized with retention of bioactivity.
Human MD2 deficiency—an inborn error of immunity with pleiotropic features
Authors: Yue Li, Ziqi Yu, Madlin Schenk, Irena Lagovsky, David Illig, Christoph Walz, Meino Rohlfs, Raffaele Conca, Aleixo M. Muise, Scott B. Snapper, Holm H. Uhlig, Ben Zion Garty, Christoph Klein, Daniel Kotlarz
Journal: Journal of Allergy and Clinical Immunology (2022)
Assessment of infant position and timing of stylet removal to improve lumbar puncture success in neonates (NeoCLEAR): an open-label, 2 × 2 factorial, randomised, controlled trial
Authors: Andrew S J Marshall, Alexandra Scrivens, Jennifer L Bell, Louise Linsell, Pollyanna Hardy, Jean Yong, Rachel Williams, Eleri Adams, Manish Sadarangani, Edmund Juszczak, Charles C Roehr
Journal: The Lancet Child & Adolescent Health (2022)
Lipid carriers for mRNA delivery
Authors: Wanting Zhang, Yuxin Jiang, Yonglong He, Hamza Boucetta, Jun Wu, Zhongjian Chen, Wei He
Journal: Acta Pharmaceutica Sinica B (2022)

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.
Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study
Authors: Paolo A Ascierto, Daniil Stroyakovskiy, Helen Gogas, Caroline Robert, Karl Lewis, Svetlana Protsenko, Rodrigo P Pereira, Thomas Eigentler, Piotr Rutkowski, Lev Demidov, Natalia Zhukova, Jacob Schachter, Yibing Yan, Ivor Caro, Christian Hertig, Cloris Xue, Lieke Kusters, Grant A McArthur, Ralf Gutzmer
Journal: The Lancet Oncology (2022)
Dynamic tagging to drive arginine nano-assembly to metabolically potentiate immune checkpoint blockade therapy
Authors: Jie Zang, Yushan Yang, Xiao Zheng, Yan Yang, Yuge Zhao, Zhe Miao, Tingting Zhang, Jingjing Gu, Yiqiong Liu, Weimin Yin, Xiaoyi Ma, Quanming Ding, Haiqing Dong, Yan Li, Yongyong Li
Journal: Biomaterials (2022)
Easy353: A Tool to Get Angiosperms353 Genes for Phylogenomic Research
Authors: Zhen Zhang, Pulin Xie, Yongling Guo, Wenbin Zhou, Enyan Liu, Yan Yu
Journal: Molecular Biology and Evolution (2022)

Abstract The Angiosperms353 gene set (AGS) consists of a set of 353 universal low-copy nuclear genes that were selected by examining more than 600 angiosperm species. These genes can be used for phylogenetic studies and population genetics at multiple taxonomic scales. However, current pipelines are not able to recover Angiosperms353 genes efficiently and accurately from high-throughput sequences. Here, we developed Easy353, a reference-guided assembly tool to recover the AGS from high-throughput sequencing (HTS) data (including genome skimming, RNA-seq, and target enrichment). Easy353 is an open-source user-friendly assembler for diverse types of high-throughput data. It has a graphical user interface and a command-line interface that is compatible with all widely-used computer systems. Evaluations, based on both simulated and empirical data, suggest that Easy353 yields low rates of assembly errors.
Ending the food bank paradox
Authors: Sabine Goodwin
Journal: BMJ (2022)

Goodwin coordinator of the Independent Food Aid NetworkBritain's food insecurity crisis was worsening before we'd heard of covid-19.In the year up to March 2020, Trussell Trust food banks had distributed 1 909 156 emergency food parcels across the UK. 1 This accounted for a fraction of wider food insecurity-according to the Department for Work and Pensions Family Resources Survey, 43% of households on Universal Credit reported severe or moderate food insecurity in that same year. 2 In January 2020, the Independent Food Aid Network (IFAN) revealed that food banks in Scotland had distributed 1,000 emergency food parcels a day over the previous 18 months. 3 Following a huge spike in need for support at the start of the pandemic, food banks saw continued, unprecedented demand through to 2021 despite a 16% reduction in food insecurity in households relying on Universal Credit because of the £20 uplift. 4 And then came the cut to Universal Credit in October 2021 resulting in increasing and relentless pressure building on households and, in turn, food banks.This pressure continues unabated as the winter sets in, and costs rise.Especially so after the recent Autumn Statement and the announcement of the chancellor's delayed approach to the bare minimum of uprating benefits in line with inflation.
Early Reversal of Right Ventricular Dysfunction after Venovenous Extracorporeal Membrane Oxygenation in Patients with COVID-19 Pneumonia
Authors: David Levy, Cyrielle Desnos, Guillaume Lebreton, Guillaume Théry, Marc Pineton de Chambrun, Pascal Leprince, Nadjib Hammoudi, Matthieu Schmidt, Alain Combes, Guillaume Hékimian
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
One‐Step Preparation of an Injectable Hydrogel Scaffold System Capable of Sequential Dual‐Growth Factor Release to Maximize Bone Regeneration
Authors: Jun Kim, Young‐Min Kim, Soo‐Chang Song
Journal: Advanced Healthcare Materials (2022)

Numerous growth factors are involved in the natural bone healing process, which is precisely controlled in a time- and concentration-dependent manner. Mimicking the secretion pattern of growth factors could be an effective means to maximize the bone regeneration effect. However, achieving the sequential delivery of various growth factors without the use of multiple materials or complex scaffold designs is challenging. Herein, an injectable poly(organophosphazene) hydrogel scaffold (IPS) encapsulating bone morphogenetic protein (BMP)-2 and TGFβ-1 (IPS_BT) is studied to mimic the sequential secretion of growth factors involved in natural bone healing. The IPS_BT system is designed to release TGFβ-1 slowly while retaining BMP-2 for a longer period of time. When IPS_BT is injected in vivo, the hydrogel is replaced by bone tissue. In addition, angiogenic (CD31 and alpha-smooth muscle actin (α-SMA)) and stemness (Nanog and SOX2) markers are highly upregulated in the early stages of bone regeneration. The IPS system developed here has promising applications in tissue engineering because 1) various amounts of the growth factors can be loaded in one step, 2) the release pattern of each growth factor can be controlled via differences in their molecular interactions, and 3) the injected IPS can be degraded and replaced with regenerated bone tissue.
Medical Marijuana Legalization and Opioid- and Pain-Related Outcomes Among Patients Newly Diagnosed With Cancer Receiving Anticancer Treatment
Authors: Yuhua Bao, Hao Zhang, Eduardo Bruera, Russell Portenoy, William E. Rosa, M. Carrington Reid, Hefei Wen
Journal: JAMA Oncology (2022)

The past decade saw rapid declines in opioids dispensed to patients with active cancer, with a concurrent increase in marijuana use among cancer survivors possibly associated with state medical marijuana legalization.
Tropoelastin Improves Post-Infarct Cardiac Function
Authors: Robert D. Hume, Shaan Kanagalingam, Tejas Deshmukh, Siqi Chen, Suzanne M. Mithieux, Fairooj N. Rashid, Iman Roohani, Juntang Lu, Tram Doan, Dinny Graham, Zoe E. Clayton, Eugene Slaughter, Eddy Kizana, April S. Stempien-Otero, Paula Brown, Liza Thomas, Anthony S. Weiss, James J.H. Chong
Journal: Circulation Research (2022)

Myocardial infarction (MI) is among the leading causes of death worldwide. Following MI, necrotic cardiomyocytes are replaced by a stiff collagen-rich scar. Compared to collagen, the extracellular matrix protein elastin has high elasticity and may have more favorable properties within the cardiac scar. We sought to improve post-MI healing by introducing tropoelastin, the soluble subunit of elastin, to alter scar mechanics early after MI.We developed an ultrasound-guided direct intramyocardial injection method to administer tropoelastin directly into the left ventricular anterior wall of rats subjected to induced MI. Experimental groups included shams and infarcted rats injected with either PBS vehicle control or tropoelastin. Compared to vehicle treated controls, echocardiography assessments showed tropoelastin significantly improved left ventricular ejection fraction (64.7±4.4% versus 46.0±3.1% control) and reduced left ventricular dyssynchrony (11.4±3.5 ms versus 31.1±5.8 ms control) 28 days post-MI. Additionally, tropoelastin reduced post-MI scar size (8.9±1.5% versus 20.9±2.7% control) and increased scar elastin (22±5.8% versus 6.2±1.5% control) as determined by histological assessments. RNA sequencing (RNAseq) analyses of rat infarcts showed that tropoelastin injection increased genes associated with elastic fiber formation 7 days post-MI and reduced genes associated with immune response 11 days post-MI. To show translational relevance, we performed immunohistochemical analyses on human ischemic heart disease cardiac samples and showed an increase in tropoelastin within fibrotic areas. Using RNA-seq we also demonstrated the tropoelastin gene ELN is upregulated in human ischemic heart disease and during human cardiac fibroblast-myofibroblast differentiation. Furthermore, we showed by immunocytochemistry that human cardiac fibroblast synthesize increased elastin in direct response to tropoelastin treatment.We demonstrate for the first time that purified human tropoelastin can significantly repair the infarcted heart in a rodent model of MI and that human cardiac fibroblast synthesize elastin. Since human cardiac fibroblasts are primarily responsible for post-MI scar synthesis, our findings suggest exciting future clinical translation options designed to therapeutically manipulate this synthesis.
Neoadjuvant mFOLFIRINOX vs mFOLFIRINOX Plus Radiotherapy in Patients With Borderline Resectable Pancreatic Cancer—The A021501 Trial
Authors: William A. Hall, Douglas B. Evans, Susan Tsai
Journal: JAMA Oncology (2022)

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